Chagas' disease, caused by the unicellular parasite Trypanosoma cruzi, represents a major health problem affecting vast areas of the American continent. Very little work has been done with the insect-borne, metacyclic form of the parasite (which causes natural infections). Hence our knowledge about host interaction with this form is very limited. The combination of expertise and interests to undertake basic research on insect-borne T. cruzi is given at Michigan State University and is exploited in this proposal to address important aspects of mammalian host infection with the virulent metacyclic organisms. We propose to: a) study the ability of insect-derived T. cruzi to rid itself of specific anti-T. cruzi antibodies in order to evade deleterious effects of immunological reactions; b) establish whether metacyclic T. cruzi insensitive to antibody-dependent complement-mediated lysis represent a subpopulation (clones, differentiation forms?) of resistant organisms or parasites shedding off antibody or complement deposits before irreversible membrane damage can take place; c) determine if unelicited or activated macrophages can destroy insect-derived T. cruzi; d) establish whether the preferential tissue tropism of different strains of T. cruzi - a property associated with production of pathological patterns of Chagas' disease - is defined by the ability of metacyclic forms to more readily associate with the surface components of certain host cell types; and e) examine the effects of lectin-induced and enzymatically caused alterations of the surface of host cells and metacyclic T. cruzi on cell infection. The proposed research is expected to improve our understanding of the mechanisms of host defense against natural T. cruzi infection and of parasite association with host cells. The information to be gained will contribute to the development of effective means of prevention and eradication of Chagas' disease.